ES2701082T3 - Enaminoketones containing CF3O and its use for the preparation of pyrazoles containing CF3O - Google Patents

Abstract

Process for preparing an enaminoketone of formula I ** Formula ** in which R1 is C5-C10 aryl, optionally substituted with 1 to 5 halogen atoms, or C5-C10 aryl having one, two or more heteroatoms selected from oxygen and nitrogen, and R2 and R3 are, independently, C1-C6 alkyl, C5-C10 aryl, C5-C10 aryl having one, two or more heteroatoms selected from oxygen and nitrogen, or together form a ring of 5 or 7 members comprising (A) reacting a CF3O-ketone of the formula II ** Formula ** in which R1 is as defined above with an aminoformylation reagent, in which the alkyl groups are linear, branched hydrocarbon groups or cyclics that may optionally have one, two or more heteroatoms chosen from oxygen, nitrogen, phosphorus and sulfur and may be optionally substituted with additional groups chosen from groups -R ', halogen (-X), alkoxy (-OR'), thioether or mercapto (-SR '), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR '), cyano (-CN), acyl (- (C = O) R') and amide (-CONR'2), being R 'hydrogen or a C1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur, and in which the aryl groups are aromatic hydrocarbon groups that may have one, two or more heteroatoms chosen from oxygen and nitrogen and may be optionally substituted with additional groups chosen from groups -R ', halogen (-X), alkoxy (-OR'), thioether or mercapto (-SR '), amino (-NR'2), silyl ( -SiR'3), carboxyl (-COOR '), cyano (-CN), acyl (- (C = O) R') and amide (-CONR2 '), where R' is hydrogen or a C1-12 alkyl group that It may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur.

Description

DESCRIPTION

Enaminoketones containing CF ³ O and its use for the preparation of pyrazoles containing CF ³ O

The present invention relates to novel enaminoketones containing a CF ³ O group, to novel pyrazole derivatives containing a CF ³ O group as well as to a novel process for their preparation comprising aminoformylation of CF ³ O-ketones and cyclization of the CF ³ O-enaminoketones obtained with hydrazines to give trifluoromethoxy pyrazoles.

Fluoride as a substituent in active ingredients plays a significant and increasingly important role. The largest group of fluorinated pesticides are compounds containing a trifluoromethyl group (primarily aromatic rings), followed by aromatic compounds containing at least one fluorine atom isolated. There are only five pesticides that contain OCF ³ groups on the market. It is estimated that the number of fluorinated compounds currently in development represents approximately 35-50% of all active ingredients in development as described in The pesticide manual, XIII edition; British crop protection council, 2003.

For the preparation of trifluoromethoxy-substituted arenes, the chlorination of aromatic methyl groups and the exchange with fluorine can be used, as described in Yagupol'skii, L. M. Dokl. Akad. Nauk SSSR.

When aryl formates are treated with sulfur tetrafluoride, (trifluoromethoxy) arenes are obtained with yields ranging from 9-81% as described in Sheppard, W. A. J. Org. Chem. 1964, 29, 1-11.

Fluoridation by oxidative fluorodesulphurization allows the conversion of dithiocarbonates (xanthogenates) with a large excess of hydrogen fluoride-pyridine and 1,3-dibromo-5,5-dimethylhydrantoin to give (trifluoromethoxy) arenes with moderate to excellent yields as disclosed in Kuroboshi, M .; Suzuki, K .; Hiyama, T. Tetrahedron Lett. 1992, 33, 4173-4176; Kanie, K .; Tanaka, Y .; Suzuki, K .; Kuroboshi, M .; Hiyama, T. Bull. Chem. Soc. Japan 2000, 73, 471-484; Kuroboshi, M .; Kanie, K .; Hiyama, T. Adv. Synth Catal. 2001, 343, 235-250 and Shimizu, M .; Hiyama, T. Angew. Chem. Int. Ed. 2005, 44, 214-231.

Obviously, the main synthesis of trifluoromethyl esters would be the direct introduction of all the OCF ³ residue. This was initially performed by radical condensation of olefins and trifluoromethyl hypofluorite (Rozen, S. Chem. Rev. 1996, 96, 1717-1736) which is highly dangerous and toxic. Then numerous attempts to carry out the trifluoromethoxylation with trifluoromethoxide salts failed since, in general, the CF ³ O- anion collapses in fluoride and fluorophosgene even at low temperature.

DE 10 2007 036702 A1 refers to combinations of synergistic herbicides comprising a herbicide from the group of pyrazolylphenyl derivatives which optionally contain a CF ³ O- group as a substituent. DE 102006 050516 A1 refers to dihydropyrazolone derivatives which optionally contain a CF ³ O- group and to processes for their synthesis for use as medicaments. None of these documents contains information about the preparation procedures of CF ³ O- derivatives or disclose references indicating how said CF ³ O- group can be introduced into the pyrazole moiety or its precursors.

At present, there is no procedure that can be applied in a general way that allows the preparation of trifluoromethoxy pyrazoles. Due to the importance of heterocyclic structures in agrochemical ingredients and the use of fluorine atoms and fluorinated groups in general, the possibility of preparing OCF ³ -heterocycles will lead to new ingredients hitherto unknown.

There is therefore a strong need for generally applicable procedures for the preparation of pyrazoles containing -OCF ³ .

Therefore, an object of the present invention is to provide a generally applicable and economically viable process that can be implemented on an industrial scale for the preparation containing -OCF ³ . The problem has been solved according to the present invention by a process for the preparation of trifluoromethoxy pyrazoles of formula V-1 or V-2 by first preparing functionalized enaminoketones of formula (I) and then transforming these functionalized enaminoketones into the trifluoromethoxy-pyrazoles of formula V-1 or V-2.

In one aspect, the present invention thus relates to a process for the preparation of an enaminoketone of formula I

in which

R 1 is C ⁵ -C ¹⁰ aryl, optionally substituted with 1 to 5 halogen atoms, or C ⁵ -C ¹⁰ aryl having one, two or more heteroatoms selected from oxygen and nitrogen, and

R2 and R3 are, independently, C ¹ -C ⁶ alkyl, aryl C ⁵ -C ¹⁰ aryl C ⁵ -C ¹⁰ having one, two or more selected from oxygen and nitrogen heteroatoms, or together form a 5- to 7 members comprising

(A) reacting a CF ³ O-ketone of formula II

wherein R1 is as defined above

with an aminoformylation reagent,

wherein the alkyl groups are linear, branched or cyclic hydrocarbon groups, which may have one, two or more heteroatoms chosen from oxygen, nitrogen, phosphorus and sulfur and, optionally, may be substituted with additional groups chosen from -R 'groups , halogen (-X), alkoxy (-OR '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR '), cyano (-CN) ), acyl (- (c = O) R ') and amide (-CONR'2), where R' is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur , Y

wherein the aryl groups are aromatic hydrocarbon groups which may have one, two or more heteroatoms chosen from oxygen and nitrogen and may be optionally substituted with additional groups selected from -R ', halogen (-X), alkoxy (-OR) groups '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR '), cyano (-CN), acyl (- (C = O) R ') and amide (-CONR2'), where R 'is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur. According to a preferred embodiment of the process of the invention for the preparation of an enaminoketone of formula I,

R1 in formula I or II is 2-furyl, phenyl, or phenyl substituted with one or two chlorine atoms and

R and R in formula I are independently C ¹ -C ⁶ alkyl.

According to an even more preferred embodiment of the process of the invention for the preparation of an enaminoketone of formula I,

R1 in formula I or II is 2-furyl, phenyl, chlorophenyl or dichlorophenyl and

R and R in formula I are C ¹ alkyl.

The present invention also relates to a process for the preparation of trifluoromethoxy pyrazoles of formulas V-1 or V-2

in which

R1 is as defined above

R 4 is H, or C ¹ -C ⁶ alkyl

which comprises

(A) reacting a CF ³ O-ketone of formula II

wherein R1 is as defined above

with an aminoformylation reagent to give an enaminoketone of formula I

in which

R1, R2 and R3 are as defined above

Y

(B) reacting the enaminoketone of formula (I) with a hydrazine of formula IV

R4-NH-NH2 (IV)

wherein R4 is as defined above,

wherein the alkyl groups are linear, branched or cyclic hydrocarbon groups which may optionally have one, two or more heteroatoms chosen from oxygen, nitrogen, phosphorus and sulfur and may be optionally substituted with additional groups chosen from -R ', halogen groups (-X), alkoxy (-OR '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR '), cyano (-CN), acyl (- (C = O) R ') and amide (-CONR'2), where R' is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur, and

wherein the aryl groups are aromatic hydrocarbon groups which may have one, two or more heteroatoms chosen from oxygen and nitrogen and may be optionally substituted with additional groups selected from -R ', halogen (-X), alkoxy (-OR) groups '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR '), cyano (-CN), acyl (- (C = O) R ') and amide (-CONR2'), where R 'is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur.

The present invention also relates to a process for the regioselective preparation of trifluoromethoxy pyrazoles of formula V-1

in which

R1 and R4 are as defined above

which comprises

(A) reacting a CF ³ O-ketone of formula II

in which

R1 is as defined above

with an aminoformylation reagent to give an enaminoketone of formula I

in which

R1, R2 and R3 are as defined above

Y

(B) reacting the enaminoketone of formula (I) with a hydrazine of formula IV

R4-NH-NH2 (IV)

in which

R4 is as defined above, with the proviso that R4 is not hydrogen

wherein (B) is carried out in a solvent selected from the group consisting of methanol, ethanol and trifluoroethanol,

wherein the alkyl groups are linear, branched or cyclic hydrocarbon groups which may optionally have one, two or more heteroatoms chosen from oxygen, nitrogen, phosphorus and sulfur and may be optionally substituted with additional groups chosen from -R ', halogen groups (-X), alkoxy (-OR '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-Co Or '), cyano (-CN) , acyl (- (C = O) R ') and amide (-CONR'2), where R' is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur, Y

wherein the aryl groups are aromatic hydrocarbon groups which may have one, two or more heteroatoms chosen from oxygen and nitrogen and may be optionally substituted with additional groups selected from -R ', halogen (-X), alkoxy (-OR) groups '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR '), cyano (-CN), acyl (- (C = O) R ') and amide (-CONR2'), where R 'is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur.

According to a preferred embodiment of the processes of the invention for the preparation of trifluoromethoxy pyrazoles of formulas V-1 or V-2 or of regioselective preparation of trifluoromethoxy pyrazoles of formula V-1, R4 in formulas IV, V-1, or V- 2 is H, or Ci alkyl.

Step (A) comprises reacting trifluoromethoxyketones according to formula (II) with an aminoformylation reagent according to the following reaction scheme 1:

The trifluoromethoxyketones of the formula (II) are commercially available or can be prepared according to the procedure described in: Marrec, et al. Advanced Synthesis & Catalysis (2010), 352 (16), 2831-2837, WO 2009141053 A120091126, DE 102008024221, Marrec, et al. Journal of Fluorine Chemistry (2010), 131 (2), 200-207. The trifluoromethoxyketones of the formula (II) can be prepared in two stages starting from the corresponding methyl ketones. First, methyl ketones are directly added by the following procedures in the literature (Synthesis 2007, 3113-3116, Tetrahedron Lett, 2006, 47, 6883-6886). The resulting a-iodomethyl ketones then react with trifluoromethyltriflate, in the presence of AgF, to carry out the replacement of the iodine with the CF ³ O group.

It has surprisingly been found that 2- (trifluoromethoxy) ketones react mildly, for example, with dimethylformamide dimethylacetal to give the novel CFaO-enaminones.

For aminoformylation, the following reagents can be used: dimethylformamide dimethylacetal, dimethylformamide diethylacetal, phenethylformamide dimethylacetal or DMF / POCI ³ (which are the precursors of compound III-2 by means of a Vilsmeier reaction). These reagents are available commercially. According to a particularly preferred embodiment of the present invention, dimethylformamide diethylacetal is used as the aminoforming reagent.

Thus, according to another embodiment of the present invention, the aminoformylation reagent used for (A) is selected from a compound of the formula III-1

wherein R 2 and R 3 are as defined above and R 5 and R 6 are C ¹ -C ⁶ alkyl and

a compound of formula III-2

R2

\

N + = CH-Cl Z- (III-2)

R3 ^

wherein R2 and R3 are as defined above.

According to another embodiment of the present invention, (A), as described above, is carried out at a temperature of from 50 ° C to 150 ° C. More preferably, (A) is carried out at a temperature of from 80 ° C to 120 ° C.

According to another embodiment of the present invention, (A) is carried out in a solvent selected from DMF, toluene, xylenes, chlorobenzenes and dimethylacetamide.

According to another further embodiment of the present invention, the reaction time is 3-10 h. More preferably, the reaction time is 4-5 h.

Stage (B) Cycling

Step (B) comprises converting enaminoketones of the formula (I) to trifluoromethoxy pyrazoles of the formula (V-1 or V-2) by cyclization with hydrazines of the formula (IV) according to the following scheme.

(I) (IV) (V-1) (V-2)

Scheme 2 R1, R2, R3, and R4 are as defined above.

With methylhydrazine, the 2 pyrazoles were regioisomeric in a ratio of 60:40 in acetic acid. According to a preferred embodiment of the present invention, the process of regioselective preparation of 1-methyl-4-trifluoromethoxy-pyrazoles is carried out using a less acid solvent, selected from methanol, ethanol and trifluoroethanol.

According to another embodiment of the present invention, the cyclization (B) is carried out in different solvents selected from alcohols, preferably methanol, ethanol or isopropanol, nitriles, preferably acetonitrile or butyronitrile, amides, preferably dimethylformamide or dimethylacetamide, and organic acids , preferably formic acid or acetic acid. The most preferred solvents for the cyclization (B) are methanol and ethanol.

According to another embodiment of the present invention, the cyclization (B) is carried out at a temperature ranging from 0 ° C to 50 ° C, more preferably at a temperature ranging from 15 ° C to 30 ° C, more preferably at room temperature.

According to another embodiment of the present invention, pyrazoles of the formula (I) can be further transformed into novel pyrazolic acids having a CF ³ O group, if R 1 is 2-Furyl (Scheme 3).

Scheme 3

Thus, the present invention further relates to a process for the preparation of trifluoromethoxy pyrazole acids of formula VI

wherein R 4 is as defined above, which comprises oxidizing a compound of formula V-1, wherein R 1 is 2-furyl and R 4 is as defined above.

According to another embodiment of the present invention, the trifluoromethoxy pyrazole acids of formula VI are obtained by oxidation of the compound of formula V-1, wherein R 1 is 2-furyl and R 4 is as defined above, using an oxidant selected from RuCl ³ / NaIO ⁴ , RuÜ ⁴ , O ³ , KMnÜ ⁴ and CrO ³ .

According to a further embodiment of the present invention, if the RuCl2 / NaIO system is used, 0.05 equivalents of RuCl3 and 10 equivalents of NaIO4 are used per 1 equivalent of pyrazole.

The choice of solvent for the reaction of Scheme 3 is very important. This will be inert towards the oxidant. According to one embodiment of the present invention, the preparation process of trifluorometoxipirazólicos acids of formula VI is carried out in a solvent selected from hexane / AcOEt / H2O, CCU / ^CH3CN / H2O, H2O / MeCN / AcOEt, and H2O / CH2Cl2 / MeCN. Most preferred is the use of hexane / AcOEt / H2O. Preferred proportions are 1/1/2 for a mixture of hexane / AcOEt / H2O and 2/2/3 for a mixture of CCl4 / CH3CN / H2O.

The oxidation is carried out at a temperature ranging from 0 ° C to 50 ° C, more preferably at a temperature ranging from 10 ° C to 30 ° C, most preferably at room temperature.

The present invention also relates to a compound of formula I

in which

R1, R2 and R3 are as defined above.

The present invention also relates to a compound of the formulas V-1 or V-2

wherein R ¹ and ⁴ R are as defined above.

The present invention also relates to a compound of formula V-1

wherein R 'and R, 44 are as defined above.

The present invention also relates to a compound of formula VI

in which

R4 is as defined above.

General definitions

In relation to the present invention, the term halogen (X) includes, unless otherwise defined, those elements that are chosen from the group consisting of fluorine, chlorine, bromine and iodine, preferably using fluorine, chlorine and bromine and fluorine and chlorine are particularly preferably used.

Groups suitably substituted may be mono- or polysubstituted, it being possible for the substituents in the polysubstitutions to be the same or different.

Alkyl groups substituted with one or more halogen atoms (-X), for example, of trifluoromethyl (CF ³ ), difluoromethyl (CHF ² ), CF ³ CH ² , ClCHh, CF ³ CCl ² and CHF ² CCl ^{2 are} chosen.

Alkyl groups in relation to the present invention are, unless otherwise defined, linear, branched or cyclic hydrocarbon groups which may optionally have one, two or more heteroatoms chosen from oxygen, nitrogen, phosphorus and sulfur. In addition, the alkyl groups according to the invention can be optionally substituted with additional groups chosen from groups -R ', halogen (-X), alkoxy (-OR'), thioether or mercapto (-SR '), amino (-NR) '2), silyl (-SiR'3), carboxyl (-COOR'), cyano (-CN), acyl (- (C = O) R ') and amide (-CONR'2), where R' is hydrogen or a C ^1-12 alkyl group, preferably a C ^2-10 alkyl group, particularly preferably a C ^3-8 alkyl group, which may optionally have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur.

The definition C ^1-12 alkyl comprises the broader range defined herein for an alkyl group. Specifically, this definition comprises, for example, the meanings methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and t-butyl, n-pentyl, n-hexyl, 1,3-dimethylbutyl , 3,3-dimethylbutyl, n-heptyl, nnonyl, n-decyl, n-undecyl and n-dodecyl.

Aryl groups in relation to the present invention are, unless otherwise defined, aromatic hydrocarbon groups which may have one, two or more heteroatoms chosen from oxygen, nitrogen, phosphorus and sulfur and may be optionally substituted with additional groups chosen from groups -R ', halogen (-X), alkoxy (-OR'), thioether or mercapto (-SR '), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR' ), cyano (-CN), acyl (- (C = O) R ') and amide (-CONR2'), where R 'is hydrogen or a C ^1-12 alkyl group, preferably a C ^2-10 alkyl group, particularly preferably a C ^3-8 alkyl group, which may have one or more heteroatoms selected from nitrogen, oxygen, phosphorus and sulfur.

The definition of C ^5-18 aryl groups having one, two or more heteroatoms selected from oxygen and nitrogen are chosen, for example, from the group consisting of 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, -isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-imidazolyl, 4-imidazolyl, 1,2,4-oxadiazole -3-yl, 1,2,4-oxadiazol-5-yl, 1,2,4-triazol-3-yl, 1,3,4-oxadiazol-2-yl, and 1,3,4-triazole- 2-yl; 1-pyrrolyl, 1-pyrazolyl, 1,2,4-triazol-1-yl, 1-imidazolyl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl; 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1,3,5-triazin-2-yl and 1,2,4-triazin-3-yl.

The alkyl groups may also have one or more heteroatoms which, unless defined otherwise, are selected from nitrogen, oxygen, phosphorus and sulfur. In this sense, the heteroatoms replace the atoms of carbon indicated.

The compounds according to the invention can exist, if appropriate, as mixtures of different possible isomeric forms, in particular of stereoisomers, such as, for example, E and Z isomers, threo and erythro isomers, and optical isomers, although, if if appropriate, also tautomers. Both the E and Z isomers, as well as the threo and erythro isomers, and also the optical isomers, any mixture of these isomers, and the possible tautomeric forms are disclosed and claimed.

Experimental part

a-Direct iodination of aromatic ketones (Synthesis of educts for the synthesis of compounds of formula II):

CuO (1.0 eq.) And I2 (1.0 eq.) Finely pulverized were added to a well-stirred solution of the ketone in anhydrous MeOH (C = 0.25M). The mixture was stirred for 5 min and then brought to reflux. After the disappearance of the reagent (controlled by TLC), the mixture was filtered and the solvent was removed under reduced pressure. The residue was poured into 10% Na ² S ² O ³ solution (10 ml / mmol of ketone), the mixture was extracted with AcOEt (3x) and the organic phase was dried (Na ² SO ⁴ ). Removal of the solvent and purification of the residue by column chromatography provided the desired products (Synthesis 2007, 3113-3116).

The ketone (1.0 eq.) Was heated together with I ² (4.0 eq.) In DME (C = 0.2M) in a round bottom flask at an oil bath temperature of 90 ° C for 3 hours. h. The contents were then cooled and extracted with AcOEt (2x). The combined extract was washed with Na ² S ² O ³ to remove unreacted iodine. The extract was then washed with brine (10 ml), dried over MgSO ⁴ and concentrated. The crude product was purified by chromatography on silica gel and the corresponding a-iodine product was isolated (Tetrahedron Lett, 2006, 47, 6883-6886).

2- (Iodoacetyl) furan

Brown oil (at 25 ° C). 1 H-NMR (300 MHz, CDCh): 8 = 7.63 (dd, J = 1.8 / 0.9 Hz, 1H), 7.32 (dd, J = 3.6 / 0.9 Hz, 1H ), 6.58 (dd, J = 3.6 / 1.8 Hz, 1H), 4.24 (s, 2H). 13 C NMR (75 MHz, CDCla): 8 = 181.9, 149.6, 146.9, 118.8, 112.8, 0.6.

1- (Iodoacetyl) -3,5-dichlorobenzene

Brown oil (at 25 ° C). 1 H NMR (300 MHz, CDCh): 8 = 7.82 (d, J = 1.8 Hz, 2H), 7.55 (dd, J = 1.8 / 1.8 Hz, 1H), 4, 34 (s, 3H). 13 C NMR (75 MHz, CDCls): 8 = 190.2, 139.1, 135.7, 135.6, 133.2, 127.2, 0.9.

1- (Iodoacetyl) -2,3-dichlorobenzene

Brown oil (at 25 ° C). 1 H NMR (300 MHz, CDCls): 8 = 7.49 (dd, J = 8.1 / 1.5 Hz, 1H), 7.35 (dd, J = 7.5 / 1.5 Hz, 1H ), 7.22 (dd, J = 8.1 / 7.5 Hz, 1H), 4.33 (s, 2H). 13 C NMR (75 MHz, CDCls): 8 = 194.3, 138.1, 133.7, 132.6, 128.8, 127.7, 127.5, 6.1.

Nucleophilic trifluoromethoxylation with TFMT and AgF (Synthesis of compounds of formula II):

In a 10 ml round bottom flask, equipped with a rubber septum and a magnetic stirrer, AgF (1.1 eq.) Was introduced. Under an argon atmosphere, CH ³ CN (C = 0.5M) was added anhydrous and the heterogeneous mixture was cooled to -30 ° C. TFMT (1.1 eq., 300 pl / mmol of iodoacetyl aromatic compound was then added, the vessel closed tightly (autogenous pressure of COF ² is necessary for the reaction to proceed) and the reaction mixture was stirred for 2 hours. at -30 ° C. After adding the electrophile (1.0 eq., pure when liquid or dissolved in the minimum of CH ³ CN when it is oil or solid) by means of a gas tight syringe, stirring was continued -30 ° C for 30 min and then at ta for 24 h (in the dark) Finally, the vessel was depressurized and the reaction mixture was filtered over Celite® The filtrate was concentrated in vacuo, the residue was dissolved in DCM , washed with brine, dried over MgSO ⁴ , filtered and concentrated in vacuo Purification by chromatography on silica gel finally gave the corresponding trifluoromethyl ether (J. Fluorine Chem. 2010, 131, 200-207).

1-phenyl-2- (trifluoromethoxy) ethanone

Yellow oil 1 H NMR (300 MHz, CDCh): 8 = 7.91 (m, 2H); 7.65 (m, 1H); 7.52 (m, 2H); 5.18 (s, 2H). 13 C NMR: 190.2; 134.4; 133.8; 129.1; 127.9; 121.8 (q, J = 256.3); 68.4 (q, J = 2.9). 13 F NMR (282 MHz, CDCh): 8 = -61.44 (s, CF ³ )

1- (2-Furyl) -2- (trifluoromethoxy) ethanone

Brown oil (at 25 ° C). 1 H-NMR (300 MHz, CDCh): 8 = 7.63 (dd, J = 1.5 / 0.6 Hz, 1H), 7.35 (dd, J = 3.6 / 0.6 Hz, 1H ), 6.61 (dd, J = 3.6 / 1.5 Hz, 1H), 5.01 (s, 2H). 13 C NMR (75 MHz, CDCh): 8 = 179.4, 150.1, 147.2, 121.6 (q, 1JC-F = 255.0), 118.8, 112.8, 67.6 (q, 3JC-F = 3.0). 13 F NMR (282 MHz, CDCh): 8 = -61.65 (s).

1- (Trifluoromethoxyacetyl) -3,5-dichlorobenzene

Brown oil (at 25 ° C). 1 H NMR (300 MHz, CDCl ³ ): ⁸ = 7.74 (d, J = 1.8 Hz, 2H), 7.59 (dd, J = 1.8 / 1 ^{, 8} Hz, 1H), 5 , 12 (s, 3H). 13 C NMR (75 MHz, CDCh): ⁸ = 188.1, 136.1, 135.9, 133.9, 127.3, 126.3, 121.5 (q, 1JC-F = 255.6) , 68.1 (q, 3JC-F = 3.0). 13 F NMR (282 MHz, CDCl ³ ): ⁸ = -61.60 (s).

1- (Trifluoromethoxyacetyl) -2,3-didorobenzene

Yellow oil (at 25 ° C). 1 H NMR (300 MHz, CDCl ³ ): 8 = 7.57 (dd, J = 8.1 / 1.8 Hz, 1H), 7.33 (dd, J = 7.5 / 1.8 Hz, 1H), 7.26 (dd, J = 8.1 / 7.5 Hz, 1H), 5.07 (s, 2H). 13 C NMR (75 MHz, CDCl ³ ): 8 = 192.8, 137.1, 133.9, 133.2, 129.1, 127.7, 127.2, 121.1 (q, 1JC-F = 255 , 2), 69.7 (q, 3JC-F = 2.9). 13 F NMR (282 MHz, CDCl ³ ): 8 = -61.28 (s).

1- (Trifluoromethoxyacetyl) -3-chlorobenzene

Yellow oil (at 25 ° C). 1 H NMR (300 MHz, CDCl ³ ): 8 = 7.82 (dd, J = 1.2 / 0.9 Hz, 1H), 7.73 (ddd, J = 7.8 / 1.5 / 1 , 2 Hz, 1H), 7.54 (ddd, J = 7.8 / 1.5 / 0.9 Hz, 1H), 7.40 (dd, J = 7.8 / 7.8 Hz, 1H) 5.14 (s, 2H). 13 C NMR (75 MHz, CDCh): 8 = 188.9, 135.2, 135.0, 134.0, 130.2, 127.8, 125.8, 121.4 (q, 1JC-F = 255.1), 68.1 (q, 3JC-F = 2.9). 13 F NMR (282 MHz, CDCl ³ ): 8 = -61.63 (s).

Synthesis of enaminoketone with DMF.DMA (Synthesis of compounds of formula I):

A solution of trifluoromethoxymethyl aryl ketone or trifluoromethoxymethyl heteroaryl ketone (1.0 eq.) And N, N-dimethylformamide dimethylacetal (DMF.DMA) (10 eq.) Was brought to reflux for 5 hours (TLC controlled). The reaction mixture was cooled, concentrated in vacuo and the residue was purified by chromatography on silica gel to provide the desired pure trifluoromethoxylated enaminoketone.

(2Z or 2E) -3- (dimethylamino) -1-phenyl-2- (trifluoromethoxy) prop-2-en-1-one

Yellow oil 1 H NMR (300 MHz, CDCh): 8 = 7.60 (m, 2H); 7.47-7.33 (solid, 3H); 7.01 (broad s, 1H); 3.12 (s, 6H). 13 C NMR (75 MHz, CDCh): 8 = 188.5; 145.4; 139.4; 130.6; 128.4; 128.2; 122.9 (m,); 121.3 (q, 1JC-F = 255.0); 42.4 (s wide). 13 F NMR (282 MHz, CDCl): 8 = -58.96 (s).

(2Z or 2E) -3- (Dimethylamino) -1- (2-furyl) -2- (trifluoromethoxy) prop-2-en-1-one

Yellow oil (at 25 ° C). 1 H-NMR (300 MHz, CDCh): 8 = 7.50 (dd, J = 1.5 / 0.6 Hz, 1H), 7.46 (broad s, 1H), 7.10 (dd, J = 3.6 / 0.6 Hz, 1H), 6.61 (dd, J = 3.6 / 1.5 Hz, 1H), 3.12 (s, 6H). 13 C NMR (75 MHz, CDCh): 8 = 173.9, 151.6, 144.8, 143.5, 121.3, 121.1 (q, 1JC-F = 255.0), 116.9, 111 , 5, 43.3, 42.6. 13 F NMR (282 MHz, CDCh): 8 = -59.47 (s).

(2Z or 2E) -3- (Dimethylamino) -1- (3 ', 5'-dichlorophenyl) -2- (trifluoromethoxy) prop-2-en-1-one

Yellow solid (at 25 ° C). 1 H-NMR (300 MHz, CDCh): 8 = 7.41 (d, J = 1.8 Hz, 2H), 7.36 (dd, J = 1.8 / 1.8 Hz, 1H), 7.01 ( s broad, 1H), 3.10 (s, 6H). 13 C NMR (75 MHz, CDCh): 8 = 184.7, 145.3, 141.8, 134.7, 130.1, 126.5, 121.7, 120.9 (q, 1JC-F = 255.5), 30.7, 29.1. 13 F NMR (282 MHz, CDCh): 8 = -59.02 (s).

(2Z or 2E) -3- (Dimethylamino) -1- (2 ', 3'-dichlorophenyl) -2- (trifluoromethoxy) prop-2-en-1-one

Brown solid (at 25 ° C). 1 H NMR (300 MHz, CDCh): 8 = 7.47 (d, J = 8.1 Hz, 1H), 7.26 (dd, J = 8.1 / 7.5 Hz, 1H), 7, 18 (d, J = 7.5 Hz, 1H), 6.56 (broad s, 1H), 3.13 (broad s, 6H). 13 C NMR (75 MHz, CDCh): 8 = 183.2, 147.0, 140.2, 132.9, 130.4, 128.7, 126.4, 125.7, 122.3, 120, 6 (q, 1JC-F = 255.4), 46.8, 37.8. 13 F NMR (282 MHz, CDCh): 8 = -58.74 (s).

(2Z or 2E) -3- (Dimethylamino) -1- (3'-chlorophenyl) -2- (trifluoromethoxy) prop-2-en-1-one

Brown oil (at 25 ° C). 1 H-NMR (300 MHz, CDCh): 8 = 7.52 (broad s, 1H), 7.41 (ddd, J = 7.5 / 1.8 / 1.2 Hz, 1H,), 7.35 (ddd, J = 7.8 / 1.8 / 0.9 Hz, 1H), 7.27 (ddd, J = 7.8 / 7.5 / 2.4 Hz, 1H), 6.96 (s) width, 1H), 3.07 (s, 6H). 13 C NMR (75 MHz, CDCl ³ ): 8 = 186.4, 145.3 (broad s), 140.8, 134.0, 130.3, 129.3, 128.1, 126.2, 122 , 1 (s broad), 121.0 (q, 1JC-F = 255.1), 30.7. 13 F NMR (282 MHz, CDCh): 8 = -59.25 (s).

Preparation of trifluoromethoxylated pyrazoles (Synthesis of compounds of formula V-1 and V-2):

To a solution of trifluoromethoxylated enaminoketone (1.0 eq.) In glacial AcOH (C = 0.2M) was added hydrazine hydrate (N ² H ⁴ .H ² O) (1.0 eq.) And the resulting mixture was He stirred ta for one night. Then, an aqueous solution of AcONa (5%) was added and the mixture was extracted with DCM (3x). The organic phases were combined, washed with saturated aqueous NaHCO ³ , brine, dried over MgSO ⁴ , filtered and concentrated in vacuo. Purification by chromatography on silica gel finally provided pure trifluoromethoxylated pyrazole.

3-Phenyl-4- (trifluoromethoxy) -1H-pyrazole

White solid (at 25 ° C); Mp = 84-85 ° C; 1 H-NMR (300 MHz, CDCh): 8 = 9.69 (broad s, 1H), 7.73 (m, 2H), 7.62 (broad s, 1H), 7.47-7.37 (solid) , 3H); 13 C NMR (75 MHz, CDCh): 8 = 138.4 (broad s), 131.1 (broad s), 129.1, 128.8, 129.6 (broad s), 126.7, 120.8 (q, 1JC-F = 256.6); 13 F NMR (282 MHz, CDCl ³ ): 8 = -60.77 (s).

3- (2-Furyl) -4- (trifluoromethoxy) -1H-pyrazole

Solid orange (at 25 ° C). Mp = 85 ° C. 1 H NMR (300 MHz, CDCl ³ ): 8 = 11.45 (broad s, 1H), 7.68 (d, J = 1.2 Hz, 1H), 7.51 (dd, J = 1.8 / 0.9 Hz, 1H), 6.80 (dd, J = 3.3 / 0.9 Hz, 1H), 6.56 (dd, J = 3.3 / 1.8 Hz, 1H). 13 C NMR (75 MHz, CDCl ³ ): 8 = 144.1, 142.2, 132.2 (broad s), 129.3 (broad s), 124.9 (broad s), 120.8 (s) , 1JC-F = 252.2), 111.8, 108.8. 13 F NMR (282 MHz, CDCl ³ ): 8 = -61.00 (s).

3- (3 ', 5'-Didorophenyl) -4- (trifluoromethoxy) -1H-pyrazole

White solid (at 25 ° C). Mp = 89 ° C. 1 H NMR (300 MHz, CDCl ³ ): 8 = 11.56 (broad s, 1H), 7.68 (broad s, 1H), 7.61 (d, J = 1.8 Hz, 2H), 7 , 36 (dd, J = 1.8 / 1.8 Hz, 1H). 13 C NMR (75 MHz, CDCl ³ ): 8 = 137.8 (s broad), 135.6, 132.0, 131.9 (broad s), 128.7, 125.0, 124.9 (s) width), 120.5 (q, 1JC-F = 257.6). 13 F NMR (282 MHz, CDCl ³ ): 8 = -60.92 (s).

3- (2 ', 3'-dichlorophenyl) -4- (trifluoromethoxy) -1H-pyrazole

Yellow oil (at 25 ° C). 1 H NMR (300 MHz, CDCl ³ ): 8 = 11.13 (broad s, 1H), 7.59 (broad s, 1H), 7.51 (dd, J = 7.5 / 1.8 Hz, 1H), 7.28 (dd, J = 7.8 / 1.8 Hz, 1H), 7.22 (dd, J = 7.8 / 7.5 Hz, 1H). 13 C NMR (75 MHz, CDCl 3): 8 = 1371 (broad s), 133.9, 132.0, 131.3, 129.8 (broad s), 129.7, 127.2, 125.0 ( s wide), 120.4 (q, 1JC-F = 256.7). 13 F NMR (282 MHz, CDCla): 8 = -60.97 (s).

3- (3'-Chlorophenyl) -4- (trifluoromethoxy) -1H-pyrazole

Yellow solid (at 25 ° C). P.f. = 44 ° C. 1 H NMR (300 MHz, CDCl 3): 8 = 12.20 (broad s, 1H), 7.63 (broad s, 1H), 7.54 (broad s, 1H), 7.51 (dd, J = 7.8 / 1.8 Hz, 1H), 7.26 (dd, J = 7.8 / 1.8 Hz, 1H), 7.24 (dd, J = 7.8 / 7.8 Hz, 1H) ). 13 C NMR (75 MHz, CDCl 3): 8 = 137.8, 134.8, 130.9 (broad s), 130.5, 130.1, 128.9, 126.5, 125.7 (broad s) ), 124.7, 120.6 (q, 1JC-F = 257.0). 13 F NMR (282 MHz, CDCl 3): 8 = -61.10 (s).

Regioselective preparation of trifluoromethoxylated methylpyrazoles (Synthesis of compounds of formula V-1):

To a solution of trifluoromethoxylated enaminoketone (1.0 eq.) In absolute EtOH (C = 0.2M) was added methyl hydrazine (MeNHNH ² ) (5.0 eq.) And the resulting mixture was stirred at rt for 5 hours ( controlled by TLC). Then, the reaction mixture was concentrated in vacuo, the residue was dissolved in AcOEt, washed with water and brine, dried over Na ² SO ⁴ , filtered and concentrated in vacuo. Purification by chromatography on silica gel finally gave pure trifluoromethoxylated methylpyrazole.

3- (2-Furyl) -1-methyl-4- (trifluoromethoxy) pyrazole

Colorless oil (at 25 ° C). 1 H NMR (300 MHz, CDCl 3): 8 = 7.48 (dd, J = 1.8 / 0.9 Hz, 1H), 7.40 (d, J = 0.9 Hz, 1H), 6, 70 (dd, J = 3.3 / 0.9 Hz, 1H), 6.47 (dd, J = 3.3 / 1.8 Hz, 1H), 3.90 (s, 3H). 13 C NMR (75 MHz, CDCl 3): 8 = 145.2, 142.2, 135.0, 129.1 (broad s), 122.6, 120.6 (q, 1JC-F = 256.0) , 111.1, 108.1, 40.0. 13 F NMR (282 MHz, CDCl 3): 8 = -61.08 (s).

3- (3 ', 5'-dichlorophenyl) -4- (trifluoromethoxy) -1-methylpyrazole

Yellow oil (at 25 ° C). 1 H NMR (300 MHz CDCl 3): 8 = 7.72 (d, J = 1.8 Hz, 2H), 7.43 (d, J = 1.2 Hz, 1H), 7.30 (dd, J = 1.8 / 1.8 Hz, 1H), 3.88 (s, 3H). 1 C NMR (75 MHz, CDCl 3): 8 = 138.8, 135.1, 133.7, 130.7 (q, 3JC-F = 2.4), 127.8, 124.6, 123.0 , 120.5 (q, 1JC-F = 257.0), 40.0. 13 F NMR (282 MHz, CDCl 3): 8 = -61.20 (s).

3- (2 ', 3'-dichlorobenzyl) -4- (trifluoromethoxy) -1-methylpyrazole

White solid (at 25 ° C). P.f. = 62 ° C. 1 H NMR (300 MHz, CDCl 3): 8 = 7.51 (dd, J = 7.8 / 1.5 Hz, 1H), 7.47 (broad s, 1H), 7.33 (dd, J = 7.8 / 1.8 Hz, 1H), 7.24 (dd, J = 7.8 / 7.8 Hz, 1H), 3.93 (s, 1H). 13 C NMR (75 MHz, CDCl 3): 8 = 140.8 (broad s), 133.5, 132.3, 132.0, 131.1 (broad s), 130.7, 130.0, 127, 0.122.1, 120.4 (q, 1JC-F = 254.8), 40.0. 13 F NMR (282 MHz, CDCl 3): 8 = -61.12 (s).

3- (3'-Chlorophenyl) -4- (trifluoromethoxy) -1-methylpyrazole

Yellow oil (at 25 ° C). 1 H-NMR (300 MHz, CDCl 3): 8 = 7.83 (broad s, 1H), 7.69 (ddd, J = 6.9 / 1.8 / 1.2 Hz, 1H), 7.36 ( d, J = 1.2 Hz, 1H), 7.29 (dd, J = 7.5 / 6.9 Hz, 1H), 7.27 (dd, J = 7.5 / 1.8 Hz, 1H ), 3.80. 13 C NMR (75 MHz, CDCl 3): 8 = 140.0, 134.4, 132.6, 130.5 (q, 3JC-F = 2.4), 129.7, 127.9, 126.3 , 124.4, 122.9 (broad s), 120.5 (q, 1JC-F = 256.4), 39.7. 13 F NMR (282 MHz, CDCl 3): 8 = -61.25 (s).

Oxidation of heterocycles having a 2-furyl residue (Synthesis of compounds of formula VI):

To a solution of (2-furyl) -pyrazol (1.0 eq.) In a mixture of n-Hexane / AcOEt / H ² O (1: 1: 2, C = 0.1M) was added NaIO ⁴ (10). eq.) (can be previously dissolved in H ² O before addition), followed by RuCl 3 (0.05M aqueous solution) (0.05 eq.). The heterogeneous reaction mixture was stirred vigorously at rt overnight. The mixture was then poured into solid NaCl (4 g / mmol of heterocycle) and a minimum of water. After 10 min of vigorous stirring, the reaction mixture was extracted with AcOEt (x3) (pH = 3-4 for the combined aqueous phases). The organic phases were combined, dried over MgSO ⁴ , filtered and concentrated in vacuo to give the desired crude carboxylic acid. The reaction can also be carried out with (2-furyl) -pyridine or (2-furyl) -pyrimidine.

4- (Trifluoromethoxy) -3-carboxy-1H-pyrazole

White solid (at 25 ° C). 1 H NMR (300 MHz, (CDÅ CO): 8 = 10.66 (broad s, 1H), 7.94 (d, J = 0.9 Hz, 1H) 13 C NMR (75 MHz, (CDa) ² CO): 8 = 160.4, 134.6 (s broad), 131.2, 128.0, 121.4 (q, 1JC-F = 254.6) 13 F NMR (282 MHz, (CDa ) ² CO): 8 = -61.70 (s).

4- (Trifluoromethoxy) -3-carboxy-1-methylpyrazole

White solid (at 25 ° C). 1 H NMR (300 MHz, (CD ³ ) ² CO): 8 = 10.76 (broad s, 1H), 7.98 (s, 1H), 3.98 (s, 3H). 13 C NMR (75 MHz, (CD ³ ) ² CO): 8 = 161.3, 134.7, 134.1 (q, 3JC-F = 2.7), 125.6, 121.3 (q, 1JC-F = 254.5), 40.7. 13 F NMR (282 MHz, (CDa) ² CO): 8 = -61.86 (s).

Claims (15)

1. Process for the preparation of an enaminoketone of formula I

in which R 1 is C ⁵ -C ¹⁰ aryl, optionally substituted with 1 to 5 halogen atoms, or C ⁵ -C ¹⁰ aryl having one, two or more heteroatoms selected from oxygen and nitrogen, and R2 and R3 are, independently, C ¹ -C ⁶ alkyl, aryl C ⁵ -C ¹⁰ aryl C ⁵ -C ¹⁰ having one, two or more selected from oxygen and nitrogen heteroatoms, or together form a 5- or 7 members which comprises (A) reacting a CF ³ O-ketone of formula II

wherein R1 is as defined above with an aminoformylation reagent, wherein the alkyl groups are linear, branched or cyclic hydrocarbon groups which may optionally have one, two or more heteroatoms chosen from oxygen, nitrogen, phosphorus and sulfur and may be optionally substituted with additional groups chosen from -R ', halogen groups (-X), alkoxy (-OR '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-CO ^or R '), cyano (-CN) ), acyl (- (C = O) R ') and amide (-CONR'2), where R' is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur , Y wherein the aryl groups are aromatic hydrocarbon groups which may have one, two or more heteroatoms chosen from oxygen and nitrogen and may be optionally substituted with additional groups selected from -R ', halogen (-X), alkoxy (-OR) groups '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR '), cyano (-CN), acyl (- (C = O) R ') and amide (-CONR2'), where R 'is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur. 2. Method according to claim 1, wherein R1 is 2-furyl, phenyl, or phenyl substituted with one or two chlorine atoms and _R 2 _{and R} 3 _{are, independently, C 1 -C 6 alkyl.} 3. Procedure for the preparation of trifluoromethoxy-pyrazoles of formula V-1 or V-2

in which R1 is as defined in claim 1 or 2, and R 4 is H, or C ¹ -C ⁶ alkyl which comprises (A) reacting a CF ³ O-ketone of formula II

wherein R1 is as defined in claim 1 or 2 with an aminoformylation reagent to give an enaminoketone of formula I

wherein R1, R2 and R3 are as defined in claim 1 or 2 and (B) reacting the enaminoketone of formula (I) with a hydrazine of formula IV R4-NH-NH2 (IV) wherein R4 is as defined above, wherein the alkyl groups are linear, branched or cyclic hydrocarbon groups which may optionally have one, two or more heteroatoms chosen from oxygen, nitrogen, phosphorus and sulfur and may be optionally substituted with additional groups chosen from -R ', halogen groups (-X), alkoxy (-OR '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-COo R '), cyano (-CN) , acyl (- (C = O) R ') and amide (-CONR'2), where R' is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur, Y wherein the aryl groups are aromatic hydrocarbon groups which may have one, two or more heteroatoms chosen from oxygen and nitrogen and may be optionally substituted with additional groups selected from -R ', halogen (-X), alkoxy (-OR) groups '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR '), cyano (-CN), acyl (- (C = O) R ') and amide (-CONR2'), where R 'is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur. 4. Procedure for the regioselective preparation of trifluoromethoxy-pyrazoles of formula V-1

in which R1 is as defined in claim 1 or 2 and R4 is as defined in claim 3, with the proviso that R4 is not hydrogen, which comprises (A) reacting a CF ³ O-ketone of formula II

wherein R1 is as defined in claim 1 or 2 with an aminoformylation reagent to give an enaminoketone of formula I

wherein R1, R2 and R3 are as defined in claim 1 or 2 and (B) reacting the enaminoketone of formula (I) with a hydrazine of formula IV R4-NH-NH2 (IV) wherein R4 is as defined in claim 3, wherein (B) is carried out in a solvent selected from the group consisting of methanol, ethanol and trifluoroethanol, wherein the alkyl groups are linear, branched or cyclic hydrocarbon groups which may optionally have one, two or more heteroatoms chosen from oxygen, nitrogen, phosphorus and sulfur and may be optionally substituted with additional groups chosen from -R ', halogen groups (-X), alkoxy (-OR '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR '), cyano (-CN), acyl (- (C = O) R ') and amide (-CONR'2), where R' is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur, and wherein the aryl groups are aromatic hydrocarbon groups which may have one, two or more heteroatoms chosen from oxygen and nitrogen and may be optionally substituted with additional groups selected from -R ', halogen (-X), alkoxy (-OR) groups '), thioether or mercapto (-SR'), amino (-NR'2), silyl (-SiR'3), carboxyl (-COOR '), cyano (-CN), acyl (- (C = O) R ') and amide (-CONR2'), where R 'is hydrogen or a C ^1-12 alkyl group which may have one or more heteroatoms chosen from nitrogen, oxygen, phosphorus and sulfur. 5. Process according to any of claims 1 to 4, wherein the aminoformylation reagent used for (A) is selected from a compound of the formula III-1

wherein R 2 and R 3 are as defined in claim 1 or 2 and R 5 and R 6 are C ¹ -C ⁶ alkyl and a compound of the formula 111-2 R2 \ N + = CH-Cl Z- (III-2) R3 ^ wherein R2 and R3 are as defined in claim 1 or 2. 6. Process according to any of claims 1 to 5, wherein (A) is carried out at a temperature of from 50 ° C to 150 ° C. 7. Process according to any of claims 1 to 6, wherein (A) is carried out in a solvent selected from DMF, toluene, xylenes, chlorobenzenes and dimethylacetamide. 8. Process according to any of claims 2 to 7, wherein (B) is carried out at a temperature of from 0 ° C to 50 ° C. 9. Procedure for the preparation of trifluoromethoxy pyrazole acids of formula VI

^{wherein R4 is as defined in claim 3,} _{which comprises oxidizing a compound of formula V-1, wherein R} 1 _{is 2-Fu} 4 _{and R is as defined in} claim 3 The process according to claim 9, wherein the Compound of formula V-1 is oxidized using an oxidant selected from RuCl ³ / NaIO ⁴ , RuO ⁴ , O ³ , KMnO ⁴ and CrO ³ . The process according to claim 9 or 10, wherein the process is carried out in a solvent selected from hexane / AcOEt / H ² O, CCl ⁴ / CH ³ CN / H ² O, H ² O / MeCN / AcOEt and H ² O / CH ² Cl ² / MeCN. 12. Compound of formula I

wherein R1, R ² and R ³ are as defined in claim 1 or 2. 13. Compound of formulas V-1 or V-2

(V-2) wherein R ¹ is as defined in claim 1 or 2 and R ⁴ is as defined in claim 3. 14. Compound of formula V-1

wherein R ¹ is as defined in claim 1 or 2 and R ⁴ is as defined in claim 3. 15. Compound of formula VI

wherein R ⁴ is as defined in claim 3.